TY - JOUR
T1 - Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy
AU - Morales, Ana
AU - Painter, Thomas
AU - Li, Ran
AU - Siegfried, Jill D.
AU - Li, Duanxiang
AU - Norton, Nadine
AU - Hershberger, Ray E.
PY - 2010/5/25
Y1 - 2010/5/25
N2 - BACKGROUND-: The term peripartum cardiomyopathy (PPCM) describes dilated cardiomyopathy (DCM) without known cause that occurs during the last month of pregnancy to 5 months postpartum. A related term, pregnancy-associated cardiomyopathy (PACM), refers to DCM onset earlier in pregnancy. Multiple studies have focused on inflammatory, immunologic, and environmental causes. An alternative hypothesis is that PPCM and PACM result, in part, from a genetic cause. In this study, we sought to test the hypothesis that rare DCM-associated mutations underlie a proportion of PACM or PPCM cases. METHODS AND RESULTS-: A systematic search of our DCM database designed for family-based genetic studies was undertaken for cases associated with pregnancy and the postpartum period; in the identified cases, clinical and molecular genetic data, including exonic and near intron/exon boundaries of DCM genes, were analyzed. Of 4110 women from 520 pedigrees in the Familial Dilated Cardiomyopathy Research Project database, we identified 45 cases of PPCM/PACM. Evidence of familial clustering with DCM was present in 23 unrelated cases. Of the 45 cases, 19 had been resequenced for known DCM genes, and 6 carried mutations. Five had PPCM, of which 3 were familial with mutations found in MYH7, SCN5A, and PSEN2, and 2 were sporadic with mutations in MYH6 and TNNT2. One case had PACM and carried a mutation in MYBPC3. CONCLUSIONS-: These findings suggest that a proportion of PPCM/PACM cases results from a genetic cause.
AB - BACKGROUND-: The term peripartum cardiomyopathy (PPCM) describes dilated cardiomyopathy (DCM) without known cause that occurs during the last month of pregnancy to 5 months postpartum. A related term, pregnancy-associated cardiomyopathy (PACM), refers to DCM onset earlier in pregnancy. Multiple studies have focused on inflammatory, immunologic, and environmental causes. An alternative hypothesis is that PPCM and PACM result, in part, from a genetic cause. In this study, we sought to test the hypothesis that rare DCM-associated mutations underlie a proportion of PACM or PPCM cases. METHODS AND RESULTS-: A systematic search of our DCM database designed for family-based genetic studies was undertaken for cases associated with pregnancy and the postpartum period; in the identified cases, clinical and molecular genetic data, including exonic and near intron/exon boundaries of DCM genes, were analyzed. Of 4110 women from 520 pedigrees in the Familial Dilated Cardiomyopathy Research Project database, we identified 45 cases of PPCM/PACM. Evidence of familial clustering with DCM was present in 23 unrelated cases. Of the 45 cases, 19 had been resequenced for known DCM genes, and 6 carried mutations. Five had PPCM, of which 3 were familial with mutations found in MYH7, SCN5A, and PSEN2, and 2 were sporadic with mutations in MYH6 and TNNT2. One case had PACM and carried a mutation in MYBPC3. CONCLUSIONS-: These findings suggest that a proportion of PPCM/PACM cases results from a genetic cause.
KW - Cardiomyopathy
KW - Genetics
KW - Pregnancy complications
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U2 - 10.1161/CIRCULATIONAHA.109.931220
DO - 10.1161/CIRCULATIONAHA.109.931220
M3 - Article
C2 - 20458009
AN - SCOPUS:77953024460
SN - 0009-7322
VL - 121
SP - 2176
EP - 2182
JO - Circulation
JF - Circulation
IS - 20
ER -